Efficacy and Thrombotic Adverse Events of Romiplostim Use in Patients with Thrombocytopenia Related to Underlying Malignancies

Background: Chemotherapy-Induced Thrombocytopenia (CIT) often results in treatment delay, dose reduction, or need for alternate cancer therapy. There is no validated or approved treatment of CIT. At our institution, the thrombopoietin-receptor agonist romiplostim, is being tested in a phase II clinical trial to treat CIT (being reported separately). Further, since there is no alternative, some oncologists have been using romiplostim off-label/off study to treat CIT and prevent recurrence of CIT when chemotherapy is resumed. Raising the platelet count could potentially increase the risk of thrombosis. Therefore, as a Quality Assessment initiative, we conducted a retrospective analysis of all use of romiplostim in cancer patients at MSKCC to determine the efficacy for treatment of CIT, as well as rates of thrombosis.

Methods: We performed a retrospective review of all romiplostim use in cancer patients at MSKCC from 1/1/2010 to 4/14/2017. Patients without cancer or patients whose thrombocytopenia was due to an unrelated indication, such as ITP, Evans syndrome, underlying cirrhosis, or hereditary thrombocytopenia syndromes, were not included in this analysis. All medical records, radiology reports, and romiplostim administration records were reviewed by one or more study investigator. The study was approved by the IRB.

Results: From 1/1/2010 through 4/14/2017, romiplostim use was documented in 292 patients. We derived 239 patients with cancer-associated indications. 185 (77.4%) of patients had thrombocytopenia related to chemotherapy and/or radiation therapy. Other causes of thrombocytopenia included primary or metastatic cancer of the liver (n=21, 8.8%), bone metastases (n=16, 6.7%), immune thrombocytopenia related to lymphoma (n=11, 4.6%), or other (n=6, 2.5%). 184 patients had solid tumors (77%) and 55 had hematologic malignancy (23%).

We performed an analysis of efficacy response to romiplostim in the cohort of solid tumor patients and lymphoid malignancies (lymphoma/myeloma), the two groups with the most patients (Table 1A). The analysis of lymphoma/myeloma below does not include stem cell transplant patients. One solid tumor patient died before any followup labs were available and is not included in the analysis.

For both solid tumor and lymphoid malignancies, the mean platelet counts at least doubled by day 14. Resumption of chemotherapy was at the discretion of the treating oncologist, and beyond Day 14 the platelet counts reflected the competing effects of maintenance romiplostim support of the platelet counts and platelet suppression by chemotherapy. The majority of patients tolerated resumption of chemotherapy without reoccurrence of CIT (Data not shown).

We analyzed the rates of thrombosis, adjusted for time of exposure to romiplostim (Table 1B). The cumulative romiplostim use in the 239 patients was 129 years. There were a total of 15 venous thromboembolic events (DVT and/or PE). This calculated to 11.6% VTE events per patient-year, well within the historical rate of thrombosis in patients with metastatic cancer or lymphoma on chemotherapy (i.e. Khorana AA et al, Cancer 2013;119:648-55). In addition, no episodes of ischemic stroke or myocardial infarction were identified in the cancer patients while on romiplostim.

Discussion: In this retrospective analysis of romiplostim use in cancer patients, we found evidence of efficacy in patients with solid tumors and lymphoid malignancies. Platelet counts increased over two-fold within 14 days of initiation of romiplostim. And importantly, we did not find evidence of increased thrombotic rates compared with historical experience. How to optimally utilize romiplostim in cancer patients with thrombocytopenia is the focus of ongoing clinical research.

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